Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The localization of the neurons expressing the acetylcholinesterase gene in the rat central nervous system was studied by in situ hybridization. The striatal and nigral neurons containing acetylcholinesterase messenger RNA were especially identified. Acetylcholinesterase messenger RNA was detected in numerous areas of the central nervous system, including cholinergic areas, like striatum, nucleus basalis of Meynert, septum and diagonal band of Broca, but also non-cholinergic areas, like the cerebral cortex, the hippocampus, the cerebellum and the raphe dorsalis. In the striatum, 75% of the neurons expressing the acetylcholinesterase gene were identified as cholinergic neurons and 25% as somatostatin-producing neurons. All dopaminergic neurons of the substantia nigra pars compacta and ventral tegmental area were demonstrated to express the acetylcholinesterase gene. Our results suggest that several neuronal populations could contribute to the presence of acetylcholinesterase in the striatum: the striatal cholinergic and somatostatin-containing interneurons, the nigral dopaminergic neurons and other neurons that may be the corticostriatal, thalamostriatal and raphe-striatal neurons. This demonstrates that, especially in the striatum, acetylcholinesterase is not a specific marker of the cholinergic neurons. The diversity of the origins of striatal acetylcholinesterase suggests a multiplicity of functions for this enzyme: besides its cholinolytic actions, it may also possibly play a non-cholinolytic role in neuromodulation.
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PMID:Anatomical analysis of the neurons expressing the acetylcholinesterase gene in the rat brain, with special reference to the striatum. 775 91

Cholinergic markers, neuropeptides, and amines and their metabolites were sampled from identical specimens across 10 neocortical regions in a large sample of Alzheimer's disease (AD) cases and controls. Levels of choline acetyltransferase, acetylcholinesterase, somatostatin, corticotropin-releasing factor, serotonin, and 5-hydroxyindoleacetic acid were significantly reduced in AD versus controls. After data reduction, the most descriptive neurochemical indices were used to examine the relationship of neurochemical measures and dementia severity within the AD sample, controlling for age effects. Dementia severity ratings were based on antemortem assessments (46.9% of AD sample) and postmortem chart review (53.1% of the AD sample). Choline acetyltransferase activity was highly correlated with clinical dementia ratings across the neocortex of the AD cases. Somatostatin and corticotropin-releasing factor levels were correlated with dementia severity only when control cases were included in the analyses. None of the amines, their metabolites, or the neuropeptides quantified related significantly to dementia severity in the AD cohort. These data (a) confirm the strong association of cholinergic deficits with functional impairment in AD and show that this association is independent of age and (b) suggest that of all the neurochemical species quantified, the cholinergic indices may be unique in their association with dementia severity.
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PMID:Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits. 783 69

The acute and chronic administration of diisopropylfluorophosphate (DFP), an inhibitor of acetylcholinesterase (AChE), and of atropine, a blocker of muscarinic cholinergic receptors, did not affect somatostatin-like immunoreactivity (SLI) content in the frontoparietal cortex and hippocampus of rats. Acute and chronic DFP administration increased the number of specific 125I-Tyr11-somatostatin (125I-Tyr11-SS) receptors in synaptosomes from the frontoparietal cortex but not in those from the hippocampus and did not change the affinity constant. This increase in 125I-Tyr11-SS binding was not due to a direct effect of DFP on somatostatin (SS) receptors since no rise of binding was produced by high concentrations of DFP (10(-5) M) when added in vitro. The increase could be blocked by pretreatment with atropine. The acute administration of atropine alone had no observable effect on the number of SS receptors. However, repeated atropine administration produced a significant decrease in the 125I-Tyr11-SS binding in synaptosomes from the frontoparietal cortex but not in those from the hippocampus although the affinity constant was unchanged. The results suggest that interactions between somatostatinergic and cholinergic receptors may be important in the rat frontoparietal cortex.
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PMID:Effect of acute and chronic diisopropylfluorophosphate and atropine administration on somatostatin binding in the rat frontoparietal cortex and hippocampus. 787 Aug 67

Pirenzepine, a muscarinic antagonist probably acting via stimulation of hypothalamic somatostatin release, abolishes the growth hormone releasing hormone (GHRH)-stimulated growth hormone (GH) rise in normal subjects but only blunts it in patients with anorexia nervosa (AN). This finding suggested the existence in AN of an alteration of cholinergic system and/or somatostatinergic tone. To further investigate these mechanisms, in 11 AN women patients (age 18.8 +/- 0.9 years; BMI 13.4 +/- 0.4) we studied the GH response alone (1 microgram/Kg IV as a bolus at 0 min) and combined with pyridostigmine (PD, 120 mg orally, 60 min before GHRH administration), a cholinesterase inhibitor, or arginine (ARG 30 g infused over 30 min starting at 0 min), two compounds probably acting via inhibition of hypothalamic somatostatin (SS) release. The GH response to GHRH preceded by a previous (120 min before) neurohormone administration also was studied. All these tests also were performed in 20 normal age-matched women (age 22.0 +/- 1.8 yrs; BMI20.1 +/- 2.4). Basal serum GH levels were higher in AN patients than in normal volunteers (NV) (10.3 +/- 3.4 versus 2.8 +/- 0.3 microgram/L; p < 0.001), whereas plasma IGF-I levels were lower in AN patients than in NV (43.3 +/- 10.6 versus 172.4 +/- 13.9 micrograms/L; p < 0.00001). In AN patients, GHRH administration induced a GH rise higher, though not significantly, than that in NV [delta area under the curve (AUC) 1173.6 +/- 167.6 versus 834.6 +/- 188.1 micrograms/L/h]. The GH response to the second of two consecutive GHRH boluses was lower (p < 0.01) than that of the first one either in AN patients or in NV (67.6 +/- 27.4 and 53.1 +/- 25.7 micrograms/L/h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa. 788 Sep 38

Laminar patterns of cortical acetylcholinesterase (AChE) activity are reestablished in the adult, pharmacologically unmanipulated rat following axotomy of the medial cholinergic pathway. The extent to which trophic and/or growth promoting or inhibiting agents modulate AChE fiber reappearance is not fully understood. Such studies, however, would further clarify possible roles for these agents in neuronal plasticity in response to injury, as well as in plastic processes associated with normative functions. In the present experiments, we explored trophic modulation by intracortically infusing nerve growth factor (NGF) or somatostatin into cingulate cortex at a site distal to transection of the medial cholinergic pathway. Comparisons were made with sham-operated or noninfused transected controls, as well as with transected animals infused with renin or antibodies against NGF. Administration began 2 days after axotomy and continued at successive 3-day intervals for 4 weeks. It was found that, proximal to the lesion site, NGF increased and somatostatin decreased optical density of AChE; the number of AChE-containing fibers was unaltered compared to controls. Distal to the knife cut, both NGF and somatostatin increased number of AChE fibers but did not alter overall AChE optical density. Nonetheless, NGF produced an increase in the number of intensely staining puncta both proximal and distal to the cut. Neither renin nor anti-NGF antibodies produced statistically significant effects on optical density or number of fibers at any cortical locus studied. We conclude that NGF and somatostatin have opposite effects on the expression of AChE: whereas NGF increases AChE levels, somatostatin inhibits AChE accumulation in proximal fibers, perhaps by actions on synthesis or transport. Fiber proliferation, which only occurred distally, was affected positively by both NGF and somatostatin, indicating that neurite-promoting effects produced by both agents are confined to tissue regions where neurite extension is stimulated by axotomy. Increases in AChE-positive puncta produced by NGF, however, were not confined to regions of fiber proliferation.
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PMID:Trophic-factor modulation of cortical acetylcholinesterase reappearance following transection of the medial cholinergic pathway in the adult rat. 789 19

This study evaluated the effect of stimulating the central nervous system (CNS) with neostigmine, an inhibitor of acetylcholinesterase, on the blood lactate concentration in fed rats and in rats fasted for 48 hours. After the rat was anesthetized with pentobarbital, neostigmine was stereotaxically injected into the third cerebral ventricle. In fed rats, the central injection of neostigmine significantly increased the blood lactate level, while concomitantly increasing plasma glucagon, epinephrine and norepinephrine concentrations. Constant infusion of somatostatin throughout the experiments, to inhibit glucagon secretion from the pancreas, did not affect alterations in blood lactate by central injection of neostigmine. In adreno-medullated rats, CNS-stimulation by neostigmine still increased plasma norepinephrine significantly, however, the alteration in blood lactate was only one-third of that in intact rats. Intraperitoneal propranolol, but not phentolamine, prevented the rise in lactate. Neostigmine increased lactate in fasted rats as well as in fed rats. We conclude that in anesthetized rats, stimulation of the CNS by neostigmine increases blood lactate mainly through circulating epinephrine and partially through circulating norepinephrine or direct sympathetic nervous stimulation; glucagon does not appear to be involved in the increase in blood lactate.
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PMID:CNS regulation of blood lactate concentration in anesthetized rats. 791 Jun 51

To indirectly evaluate the hypothalamic somatostatin (SS) tone in patients with acromegaly, the effects of pyridostigmine (PD), a cholinesterase inhibitor which can inhibit hypothalamic SS secretion, on TRH-induced TSH secretion and the effects of SMS 201-995 on TSH or GH secretion were studied in acromegalic patients (31-69 yr, n = 10), normal young (21-24 yr, n = 7) and normal old male subjects (62-71 yr, n = 7). After pretreatment with PD (60 mg po, -30 min), normal young subjects showed significantly enhanced TSH responses to TRH (500 micrograms i.v., 0 min) compared to single administration of TRH, whereas normal old and acromegalic patients did not show such enhancement. Plasma TSH response to a single administration of TRH in acromegalic patients was significantly lower than that of normal young and old subjects. Although normal young and old subjects showed significantly enhanced GH responses to GHRH (100 micrograms i.v. at 0 min) after the pretreatment with PD (60 mg, -30 min), no such enhancement was observed in acromegalic patients. In contrast, the decrement in plasma TSH after SMS 201-995 administration was similar between normal subjects (5 young 5 old) and 7 acromegalic patients. Further, the maximal plasma GH decrement after administration was significantly greater in acromegalic patients than in the 5 normal young and 5 old subjects p < 0.01). In conclusion, hypothalamic SS tone does not appear to be elevated in acromegalic patients compared to normal young and probably old subjects.
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PMID:The evaluation of hypothalamic somatostatin tone using pyridostigmine and thyrotropin releasing hormone in patients with acromegaly. 791 36

Heart rate is regulated by the autonomic nervous system but little is known about the pattern of innervation of the pacemaker in the sinoatrial node, or the subpopulations of nerves involved. Therefore in this study the pacemaker was located using electrophysiological methods and the pattern of innervation established by cholinesterase staining. In subsequent experiments, subpopulations of sympathetic, sensory and parasympathetic nerves were identified. Sympathetic nerves were labelled by glyoxylic acid-induced catecholamine fluorescence or an antiserum raised against tyrosine hydroxylase (TH). These experiments showed that the entire sinoatrial node was densely innervated by sympathetic axons, the majority of which were immunoreactive for neuropeptide Y (NPY). There were a few axons which were only immunoreactive for TH. Sensory nerves which were immunoreactive for both substance P (SP) and calcitonin gene-related peptide (CGRP) were also found throughout the sinoatrial node. In the absence of a selective marker for parasympathetic neurons, hearts were extrinsically denervated by placing them in organotypic culture to allow degeneration of extrinsic axons. In this way intrinsic parasympathetic neurons could be characterised. These experiments revealed several distinct populations of parasympathetic nerves which innervated only a small, discrete part of the sinoatrial node. These populations were immunoreactive for NPY, somatostatin (SOM) or vasoactive intestinal peptide (VIP) alone, or SOM combined with NPY, SOM with dynorphin B, and SOM with SP. These results highlight a remarkable difference in the pattern of innervation of the sinoatrial node by the sympathetic and parasympathetic nervous systems. Furthermore the presence of several distinct populations of autonomic cardiac neurons indicates a further complexity in neuronal regulation of heart rate.
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PMID:Innervation of the pacemaker in guinea-pig sinoatrial node. 801 78

GH secretion is stimulated by the administration of cholinesterase inhibitors (such as pyridostigmine and neostigmine) in several species, including man. On the basis of indirect experiments, it has been postulated that this action is mediated by a decrease in hypothalamic somatostatin release. We have investigated the effect of neostigmine in sheep, since it is possible to collect hypophysial portal blood for GH-releasing hormone (GHRH) and somatostatin determination in this species under a conscious unstressed state. First, after i.v. injection of neostigmine (1 mg), a significant increase in plasma GH levels and an unequivocal potentiation of the GH response to GHRH were observed. Then, we observed that i.v. injection of neostigmine (1 mg) induced an immediate, short-lasting (30 min), and marked increase in GHRH (126.1 +/- 17 vs. 14.5 +/- 2.1 pg/ml; P < 0.01) levels in hypophysial portal blood of rams chronically implanted with perihypophysial cannulae. No change in somatostatin secretion was recorded during the same period. These data suggest that the stimulating effect of cholinergic drugs on GH secretion is mediated by stimulation of GHRH release. A direct effect of neostigmine at the level of pituitary gland is possible and may explain the potentiation of GHRH-induced GH release.
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PMID:Neostigmine stimulates growth hormone-releasing hormone release into hypophysial portal blood of conscious sheep. 809 14

Cognitive and histological alterations in human Alzheimer's disease (AD) are correlated with selective neuronal loss in nucleus basalis of Meynert. In search of an animal model of AD-linked neurochemical deficits, we examined the effects of short- (2 weeks) and long- (3 and 6 months) term lesions of the nucleus basalis magnocellularis (NBM) on somatostatinergic parameters in rat forebrain. NBM lesions were performed by unilateral injection of ibotenic acid into the NBM. Cortical choline-acetyl transferase (ChAT) activity and acetylcholinesterase staining in the NBM remained significantly decreased ipsi- as compared to contralaterally up to 6 months after the placement of the lesion. Somatostatin (SRIF) content was increased by 120% in the ipsilateral frontal cortex 6 months post-lesion but not at shorter time intervals. Levels of neuropeptide Y (which is extensively co-localized with SRIF in the forebrain) were not significantly altered after unilateral NBM lesions at any time point. A 30% decrease in SRIF binding capacity as well as a marked reduction of SRIF inhibition of adenylate cyclase, indicative of a loss of functional SRIF receptors, was observed in ipsilateral versus contralateral frontal cortex on brain tissue homogenates after short-term unilateral NBM lesion. By film radioautography, the loss in SRIF binding sites was localized to both superficial and deep layers of the frontal cortex. This loss persisted up to 3 months but was no longer apparent after 6 months due to a decrease in SRIF binding capacity on the contralateral side.
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PMID:Short- and long-term effects of nucleus basalis magnocellularis lesions on cortical levels of somatostatin and its receptors in the rat. 809 61


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